Light-activated fluorescent proteins have revolutionized imaging technologies, and with them our fundamental understanding of cellular processes (Zimmer, 2009). The use of light to control protein activities in live animals with spatiotemporal resolution unmatched by drugs has even greater potential (Miesenbock et al. 2009; Liu & Tonegawa, 2010). Optogenetic approaches utilizing natural photoreceptors have provided insights into the underpinnings of information processing in the nervous system, locomotion, awakening, neural circuits in Parkinson's disease, progression of epilepsy, etc. (Airan et al., 2009; Adamantidis et al., 2007; Cardin et al., 2009; Gradinaru et al., 2009; Sohal et al., 2009; Tønnesen et al., 2009; Tsai et al., 2009; and Gradinaru et al., 2010). Several groups have succeeded in engineering photoactivated proteins with new functions (Lee et al., 2008; Strickland et al., 2008; Tyszkiewicz and Muir, 2008; Yazawa et al., 2009; Möglich et al., 2009; Wu et al., 2009; and Georgianna & Deiters, 2010). However, the use of optogenetic approaches outside neurobiology remains very limited (reviewed in Möglich et al., 2010; Toettcher et al., 2011). The potential of using proteins activated by far-red and near-infrared (NIR) light, which penetrates animal tissues to the depths of several centimeters (Cuberddu et al., 1999; Wan et al., 1981; Byrnes et al., 2005) and therefore can be applied externally, has remained largely unexplored because of limitations in the ability to engineer such proteins with desired output activities.